Hirschsprung disease is characterized by aganglionosis of the bowel. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease), in 15%-20% of cases the aganglionosis extends proximal to the sigmoid colon (long-segment disease) and in about 5% of cases the aganglionosis affects the entire large intestine (total colonic aganglionosis).

Dominant loss-of-function variants in the RET gene account for up to 50% of familial cases of Hirschsprung disease (Attie et al 1995 Hum Mol Genet 4:1381-1386) and approximately 25% of sporadic cases (Eng and Mulligan 1997 Hum Mutat 9:97-109). Variants are located throughout the RET gene. Deletions of the entire RET gene occur in <5% of patients with Hirschsprung disease (Seri et al 1997: Hum Mutat:243-249). Incomplete penetrance and variable expressivity has been reported.

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.